Bevacizumab benefits ovarian cancer patients irrespective of timing

medwireNews: Patients with platinum-resistant ovarian cancer (PROC) gain significant survival benefit from treatment with bevacizumab, regardless of whether its given with or after chemotherapy, an exploratory analysis of AURELIA study data show.

“Early treatment of PROC with bevacizumab plus chemotherapy combination therapy ensures that most patients with this disease can benefit from anti-angiogenic therapy,” Aristotelis Bamias (University of Athens, Greece) and co-authors remark.

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“However, if this strategy has not been adopted, the use of bevacizumab after [disease progression] on chemotherapy alone for PROC may be beneficial,” they add.

During the AURELIA study, 179 women with PROC were randomly assigned to receive chemotherapy combined with bevacizumab upfront, while 182 received chemotherapy alone. Of these, 72 crossed over to receive bevacizumab after disease progression, while the remaining 110 never received the drug.

The researchers found that, compared with patients who never received bevacizumab, the risk for death was reduced by a significant 32% in those who received it upfront with chemotherapy and by 40% in those who received it after disease progression.

When the patients were grouped according to prognosis, those classified as having poor prognosis benefited more or less equally from bevacizumab given upfront (hazard ratio [HR] for overall survival [OS]=0.58 vs no bevacizumab) or after disease progression (HR=0.63).

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By contrast, among the patients with a good prognosis, greater benefit was derived from receiving bevacizumab at disease progression (HR=0.64) than in combination with chemotherapy (HR=0.91). But the researchers warn that the results should be interpreted with caution due to the limited power of the subgroup analyses.

Bamias and team also report that bevacizumab was well tolerated when it was given with or after chemotherapy, with grade 3 or higher adverse events occurring in just 7% and 3% of patients, respectively.

Writing in the Annals of Oncology, the researchers suggest that their findings may explain the lack of difference in OS in the original analysis of AURELIA data, despite a significant improvement in progression-free survival with chemotherapy plus bevacizumab versus chemotherapy alone.

“[The lack of OS benefit from the addition of bevacizumab to chemotherapy in the AURELIA trial may be partially attributed to the confounding effect of bevacizumab administration after PD in the control arm,” they write.

The authors also discuss the best time to administer bevacizumab in PROC. They say that “it is impossible to draw definitive conclusions” from their findings but emphasize the fact that 60% of patients in the chemotherapy-alone arm did not receive bevacizumab, despite having similar disease characteristics to those who did at baseline and at the time of disease progression.

They say that this was due, in some cases, to death within 12 weeks of disease progression, deterioration in ECOG performance status, and adverse events that may have prevented the use of bevacizumab.

“This observation supports the use of bevacizumab concurrently with chemotherapy in PROC at the earliest opportunity to maximise the number of patients having the opportunity to receive anti-angiogenic therapy,” Bamias et al conclude